This work has great importance as prediction of post DAAS HCC is the headache association of such revolution in the treatment of HCV-related liver disease, reaffirming the role of IL-28B SNP in progression to and of cirrhosis is expected, and the results were surprising.
The present study includes 50 HCC patients post DAAs, 50 cirrhotic patients post DAAs without HCC, and 100 normal as a control.
In our study, the distribution of the polymorphisms between the HCC group and cirrhotic group was close in both, and no significant differences were found. In the HCC group, C C genotype, T T genotype, and C T genotype were 14%, 18%, and 68% while they represented 20%, 28%, and 52% respectively in cirrhotic group (p value =0.26). As regards alleles, there were no significant differences for C and T alleles between the HCC group (48%, 52%) and cirrhotic group (46%, 54%) (p value =0.77).
These results denote a lack of association between SNP of IL-28B and HCC post DAAs. Therefore, SNP of IL-28B cannot predict the emergence of HCC after DAAs.
Salum et al. [11] reported similar results of no significance was found in SNP of IL-28B in prediction of HCC post DAAs. They found C C, T T, and C T genotypes were 31%, 6%, and 55% in HCC group while in cirrhotic group were 27%, 20%, and 26% (p value = 0.457). For alleles, they found in the HCC group C allele was 58% and T allele was 42%, while in the cirrhotic group, C allele was 53% and T alleles was 47% (p value = 0.31) which also refer to lack of significance between SNP of IL-28 and HCC post DAAs.
On the opposite side, Simili et al. [12] reported a significant association between SNP of IL-28 and HCC post DAAs. T T genotype was unfavorable and associated with a higher risk of HCC post DAAs (p value =0.024).
This conflict with the previous results is found as this study included a small number of HCC cases after DAAs of only 11 patients. Six of them had a history of HCC and were treated at least 6 months before DAAs, and 5 of them were without recurrence while a number of patients without recurrence in our study was 50 cases and in Salum et al. [11] was 65 patients.
HCV Genotype 4 is the most common genotype in Egypt while genotype 1a is the most common in Europe. Genotype distribution is important in predicting disease progression, response to therapy, progression of fibrosis, and a higher risk of HCC [13].
In our study, a significant association between SNP of IL-28B in healthy individuals and the cirrhotic group was detected (p value =0.004). A significant increase was observed in frequencies of IL-28B C C genotype in the healthy population (28%) than the cirrhotic group (20%) and in C T (64%) genotype in the healthy group than the cirrhotic group (52%). On the other hand, T T genotype was more prevalent in cirrhotic patients (28%) than controls (8%).
As regards alleles, C allele appeared to be protective against cirrhosis with 60% distribution in healthy individuals and 46% in the cirrhotic group. T allele was more prevalent in cirrhotic (54%) than the normal group (40%) (p value =0.02)
A significant increase (P < 0.0005) was observed in frequencies of IL-28B C C genotypes in the healthy population than in the cirrhotic group (48%, 13%) respectively [14].
Attallah et al. [15] found that IL-28B T T genotype is more prevalent in patients with advanced fibrosis and cirrhosis among HCV genotype 4 Egyptian patients (p value ˂0.05).
Also, Fuente et al. [16] found TT genotype in IL28B polymorphism was highly prevalent in HCV cirrhotic patients but it did not directly influence hepatocarcinogenesis.
These similar results suggest the role of SNP IL-28 in HCV disease progression and liver cirrhosis.
Limitations
Transient elastography was not done as it is very expensive for our patients. Also, the relatively small number of patients was due to the difficulty in acceptance by patients to be included in a research study in addition to the high expense of the kits.
Interpretation
Our results should be interpreted with caution because of several limitations. We recruited 200 samples in this study; the sample size of each group was relatively small which may restrict its detailed subgroup analysis by the clinical index. All participants were all from Mansoura Specialized Medical Hospital which may not stand for all the Egyptian population.
Generalizability
The fundamental experiments should be further conducted to validate our results and explore the possible mechanism.